- KSHV-associated multicentric Castleman disease (KSHV-MCD) is caused by a herpes virus known as KSHV. This disease can also cause several other cancers, including Kaposi sarcoma. People with KSHV-MCD often have symptoms like fever, weight and muscle loss, and fluid in the legs or abdomen. Tocilizumab may be able to block the chemicals in the body that cause KSHV-MCD symptoms. Researchers want to test this drug and other anti-virus drugs to find the best combination of drugs to treat KSHV-MCD.

Objectives:

- To test the effectiveness of tocilizumab with and without other anti-virus drugs for KSHV-MCD.

Eligibility:

- People at least 18 years of age who have KSHV-MCD and have certain symptoms and blood abnormalities caused by their KSHV-MCD.

Design:

Participants will be screened with a medical history and physical exam. They will also have blood tests, and a skin biopsy.

Participants will have tocilizumab injections every 2 weeks for up to 12 weeks. They will provide daily blood samples for the first 3 days of treatment.

After the sixth dose, participants will be monitored for 4 weeks to check for possible side effects.

Those whose KSHV-MCD does not improve or worsens during the study may have tocilizumab combined with two other anti-virus drugs, zidovudine and valganciclovir. These drugs are pills that will be taken four times a day for 5 days out of every 2 weeks.

Blood, urine, and saliva samples will be collected throughout the study.

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Determine the efficacy of tocilizumab in the treatment of KSHV-MCD. [ Time Frame: Evaluation of MCD clinical and biochemical response at each visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Estimate best clinical, biochemical, radiographic and overall response. [ Time Frame: Clinical and laboratory responses are assessed in aggregate and compared to baseline. ] [ Designated as safety issue: No ]

Evaluate progression-free and overall survival with tocilizumab and tocilizumab/AZT/VGC. [ Time Frame: Time interval from the date of enrollment to the date of progression from best response. ] [ Designated as safety issue: No ]

Evaluate safety and tolerability of tocilizumab alone and in combination with AZT/VGC [ Time Frame: Toxicities will be evaluated both per cycle and per patient. ] [ Designated as safety issue: Yes ]

Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are CYP3A4 substrates in patients with symptomatic KSHVMCD [ Time Frame: Cycle 1, Day 1, Day 3, Cycles 2--6 ] [ Designated as safety issue: Yes ]

Evaluate effect of tocilizumab on KS [ Time Frame: Baseline, week 7 and at off-study ] [ Designated as safety issue: No ]

HIV-infected patients should be receiving or willing to initiate an effective combination antiretroviral therapy (cART) regimen

Willingness to complete tuberculosis evaluation and start prophylactic antituberculosis therapy as soon as is medically feasible if patients have a reactive tuberculin skin test and have not completed an adequate course of prevented anti-tuberculosis therapy, following American Thoracic Society / Centers for

Disease Control recommended guidelines:

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm

Ability to understand and willingness to give informed consent

Women of child bearing potential must agree to use birth control for the duration of the study

History of greater than or equal to 2 allergic reaction or any grade anaphylactic reaction during prior administration of tocilizumab

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441063